托烷司琼通过激活大鼠脊髓α7nAChR减轻慢性神经病理性疼痛和p38MAPK表达

张雨飞; 于迪; 龚兴瑞; 侯娜; 蒙臣; 李清

doi:10.13406/j.cnki.cyxb.002952

您当前的位置：

首页 >

文章列表页 >

托烷司琼通过激活大鼠脊髓α7nAChR减轻慢性神经病理性疼痛和p38MAPK表达

基础研究 | 更新时间：2022-06-24

- 托烷司琼通过激活大鼠脊髓α7nAChR减轻慢性神经病理性疼痛和p38MAPK表达
- Tropisetron reduces chronic neuropathic pain and the expression of p38MAPK by activating α7nAChR in rat spinal cord
- 重庆医科大学学报 2022年47卷第5期页码：543-547
- 作者机构：
  
  1.锦州医科大学十堰市太和医院研究生培养基地（湖北医药学院附属医院），十堰　442000
  2.湖北文理学院附属襄阳中心医院麻醉科，襄阳　441021
  3.十堰市太和医院（湖北医药学院附属医院）麻醉科，十堰　442000
- 作者简介：
  
  张雨飞，Email：1520232406@qq.com，研究方向：神经病理性疼痛和围术期麻醉。
  李清，Email：liqing8801@163.com。
- 基金信息：
  
  国家自然科学基金青年科学基金资助项目(81700082);湖北省自然科学基金资助项目(2019CFB411)
- DOI：10.13406/j.cnki.cyxb.002952
  中图分类号： R745.4
- 纸质出版日期：2022-05-28，
  
  收稿日期：2021-01-22，
扫描看全文
张雨飞, 于迪, 龚兴瑞, 等. 托烷司琼通过激活大鼠脊髓α7nAChR减轻慢性神经病理性疼痛和p38MAPK表达[J]. 重庆医科大学学报, 2022,47(5):543-547.

Yufei Zhang, Di Yu, Xingrui Gong, et al. Tropisetron reduces chronic neuropathic pain and the expression of p38MAPK by activating α7nAChR in rat spinal cord[J]. Journal of Shanxi Agricultural Sciences, 2022,47(5):543-547.
张雨飞, 于迪, 龚兴瑞, 等. 托烷司琼通过激活大鼠脊髓α7nAChR减轻慢性神经病理性疼痛和p38MAPK表达[J]. 重庆医科大学学报, 2022,47(5):543-547. DOI： 10.13406/j.cnki.cyxb.002952.

Yufei Zhang, Di Yu, Xingrui Gong, et al. Tropisetron reduces chronic neuropathic pain and the expression of p38MAPK by activating α7nAChR in rat spinal cord[J]. Journal of Shanxi Agricultural Sciences, 2022,47(5):543-547. DOI： 10.13406/j.cnki.cyxb.002952.

摘要

目的：

探索鞘内注射托烷司琼是否通过激活α7烟碱乙酰胆碱受体（alpha 7 nicotinic acetylcholine receptor，α7nAChR）减轻坐骨神经分支选择性损伤（spared nerve injury，SNI）大鼠慢性神经病理性疼痛和p38丝裂原活化蛋白激酶（p38 mitogen-activated protein kinase，p38MAPK）表达。

方法：

体质量180~220 g的成年雄性SD大鼠，鞘内置管和模型成功后，采用随机数字表法分为5组（

=12只/每组）：假手术组、神经损伤组、托烷司琼组、α7nAChR拮抗剂methyllycaconitine citrate组（MLA组）、MLA+托烷司琼组。假手术组仅暴露右侧坐骨神经，神经损伤组、托烷司琼组、MLA组、MLA+托烷司琼组均制备右侧坐骨神经损伤模型。模型建立后第14天分别鞘内给药，于不同时间点进行疼痛行为学观察和测试。给药1 h后处死大鼠取脊髓L4~6段，采用组织免疫荧光染色观察脊髓背角α7nAChR分布和表达情况，Western blot检测α7nAChR、p-p38和p38蛋白表达量变化。

结果：

与给药前相比，托烷司琼组和MLA+托烷司琼组给药后机械缩爪阈值（paw mechanical withdrawal threshold，PMWT）和辐射热缩爪潜伏期（paw thermal withdrawal latency，PTWL）都明显升高，MLA+托烷司琼组均较托烷司琼组低。给药前后MLA组PMWT和PTWL均无明显变化；α7nAChR荧光结果显示，与假手术组阳性面积相比，神经损伤组明显降低。托烷司琼组和MLA+托烷司琼组阳性染色都明显较神经损伤组升高；Western blot结果发现托烷司琼组和MLA+托烷司琼组α7nAChR蛋白表达较神经损伤组明显增高，而p-p38蛋白表达水平与神经损伤组相比均明显降低。各组p38蛋白表达水平均无明显差异。

结论：

鞘内注射托烷司琼可减轻SNI大鼠慢性神经病理性疼痛，α7nAChR拮抗剂MLA可一定程度阻断其疼痛减轻作用。其机制可能与托烷司琼选择性激活α7nAChR从而抑制p38MAPK信号通路有关。

Abstract

Objective

To explore whether intrathecal injection of tropisetron alleviates chronic neuropathic pain and p38 mitogen-activated protein kinase (p38MAPK) expression in rats with spared nerve injury (SNI) by activating alpha 7 nicotinic acetylcholine receptor (α7nAChR) .

Methods

Adult male SD rats weighing 180-220 g were randomly divided into 5 groups (

=12/each group): sham operation group

nerve injury group

tropisetron group

α7nAChR antagonist methyllycaconitine citrate group (MLA group)

and MLA+tropisetron group. The right sciatic nerve was exposed only in the sham operation group

and the right sciatic nerve injury models were made in the nerve injury group

tropisetron group

MLA group and MLA+tropisetron group. On the 14th day after the establishment of the pain model

the drugs were administered intrathecally

and the pain behavior was observed and tested at different time. One hour after administration

the rats were sacrificed and the L4-6 segments of spinal cord were removed. The distribution and expression of α 7nAChR in spinal dorsal horn were observed by tissue immunofluorescence staining. Western blot was used to detect the changes of α7nAChR

p-p38 and p38 protein expression.

Results

The paw mechanical withdrawal threshold (PMWT) and paw thermal withdrawal latency (PTWL) in tropisetron group and MLA+tropisetron group were significantly higher than those before administration

and that in MLA+tropisetron group was lower than that in tropisetron group. There was no significant change in PMWT and PTWL in MLA group before and after administration. The immunofluorescence results of α7nAChR showed that the positive area in the nerve injury group was significantly lower than that in the sham operation group. The positive staining in tropisetron group and MLA+tropisetron group was significantly higher than that in nerve injury group. Western blot results showed that the expression of α 7nAChR in tropisetron group and MLA+tropisetron group was significantly higher than that in nerve injury group

while the expression level of p-p38 protein in tropisetron group was significantly lower than that in nerve injury group. There was no significant difference in the expression level of p38 protein among all groups.

Conclusion

Intrathecal injection of tropisetron can relieve chronic neuropathic pain in SNI rats

and α7nAChR antagonist MLA can block its pain-relieving effect to some extent. The mechanism may be related to the selective activation of α7nAChR and inhibition of p38MAPK signal pathway by tropisetron.

关键词

托烷司琼慢性神经病理性疼痛α7烟碱乙酰胆碱受体p38丝裂原活化蛋白激酶

Keywords

tropisetronchronic neuropathic painalpha 7 nicotinic acetylcholine receptorp38 mitogen-activated protein kinase

references

李鹏涛, 秦颖, 肖智. 脊髓P2X7受体激活介入曲马多对神经病理性疼痛的镇痛机制[J]. 医学研究生学报, 2018, 31(5): 459-465.

Li PT, Qin Y, Xiao Z. Activation of spinal P2X7 receptor and analgesic effect of tramadol on neuropathic pain in rats[J]. J Med Postgrad, 2018, 31(5): 459-465.

Colloca L, Ludman T, Bouhassira D, et al. Neuropathic pain[J]. Nat Rev Dis Primers, 2017, 3: 17002.

Hone AJ, McIntosh JM. Nicotinic acetylcholine receptors in neuropathic and inflammatory pain[J]. FEBS Lett, 2018, 592(7): 1045-1062.

Svensson CI, Marsala M, Westerlund A, et al. Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammation-induced spinal pain processing[J]. J Neurochem, 2003, 86(6): 1534-1544.

Wang Y, Jiang Q, Xia YY, et al. Involvement of α7nAChR in electroacupuncture relieving neuropathic pain in the spinal cord of rat with spared nerve injury[J]. Brain Res Bull, 2018, 137: 257-264.

文晓娟, 张博闻, 吴智兵. 常见SD大鼠神经病理性疼痛模型研究[J]. 医学信息, 2018, 31(1): 49-51.

Wen XJ, Zhang BW, Wu ZB. Study on the neuropathic pain model of common SD rats[J]. Med Inf, 2018, 31(1): 49-51.

沈茜, 高进, 陈萍. NMDA受体拮抗剂对神经病理性疼痛大鼠脊髓背角bFGF表达的影响[J]. 重庆医科大学学报, 2016, 41(1): 50-55.

Shen Q, Gao J, Chen P. Effect of intrathecal administration of NMDA receptor antagonist on the expression of bFGF in spinal dorsal horn of rat with neuropathic pain[J]. J Chongqing Med Univ, 2016, 41(1): 50-55.

Nasirinezhad F, Hosseini M, Karami Z, et al. Spinal 5-HT3 receptor mediates nociceptive effect on central neuropathic pain; possible therapeutic role for tropisetron[J]. J Spinal Cord Med, 2016, 39(2): 212-219.

丘玥, 陈唯韫, 王之遥, 等. 辛伐他汀对大鼠神经病理性疼痛行为学和RhoA通路表达的影响[J]. 中国疼痛医学杂志, 2016, 22(7): 493-500.

Qiu Y, Chen WY, Wang ZY, et al. The effect of simvastatin on pain behavior and the expression of rhoa pathway in neuropathic pain rats[J]. Chin J Pain Med, 2016, 22(7): 493-500.

Khalifeh S, Fakhfouri G, Mehr SE, et al. Beyond the 5-HT3 receptors: a role for α7nACh receptors in neuroprotective aspects of tropisetron[J]. Hum Exp Toxicol, 2015, 34(9): 922-931.

Fakhfouri G, Mousavizadeh K, Mehr SE, et al. From chemotherapy-induced Emesis to neuroprotection: therapeutic opportunities for 5-HT3 receptor antagonists[J]. Mol Neurobiol, 2015, 52(3): 1670-1679.

Ji L, Chen YM, Wei HX, et al. Activation of alpha7 acetylcholine receptors reduces neuropathic pain by decreasing dynorphin A release from microglia[J]. Brain Res, 2019, 1715: 57-65.

Huang Q, Mao XF, Wu HY, et al. Bullatine A stimulates spinal microglial dynorphin A expression to produce anti-hypersensitivity in a variety of rat pain models[J]. J Neuroinflammation, 2016, 13(1): 214.

Cui Y, Liao XX, Liu W, et al. A novel role of minocycline: attenuating morphine antinociceptive tolerance by inhibition of p38 MAPK in the activated spinal microglia[J]. Brain Behav Immun, 2008, 22(1): 114-123.

Zhang T, Zhang N, Zhang R, et al. Preemptive intrathecal administration of endomorphins relieves inflammatory pain in male mice via inhibition of p38 MAPK signaling and regulation of inflammatory cytokines[J]. J Neuroinflammation, 2018, 15(1): 320.

查看原文

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

5-羟色胺受体拮抗剂在预防压力过超载诱导的小鼠心肌肥大中的作用